苦参素固体脂质纳米粒的药动学和体内分布

 目的研究苦参素固体脂质体纳米粒(SLN)的动物体内行为,探讨苦参素SLN作为肝靶向给药系统的可行性。方法采用“乳化蒸发-低温凝固”法制备苦参素SLN,平均粒径104nm,表面电位-32.6mV,包封率为81.0%。将苦参素SLN悬液与苦参素水溶液分别大鼠尾静脉注射100mg·kg^-1,于不同时间尾静脉取血,测定血中苦参素浓度,提取药动学参数。将苦参素SLN悬液与苦参素水溶液小鼠尾静脉注射100mg·kg^-1,于不同时间取血、心、肝、脾、肺、肾,测定各组织中药物浓度,计算靶向指数、靶向效率及相对靶向效率等参数。结果大鼠尾静脉注射苦参素水溶液和苦参素SLN悬液100mg·kg^-1后,药动学结果显示,体内过程符合二室开放模型,与苦参素水溶液相比,苦参素SLN的t_1/2β延长5.5倍,AUC增加了3.9倍。小鼠尾静脉注射苦参素水溶液和苦参素SLN悬液100mg·kg^-1后,体内分布结果显示:苦参素SLN给药后在肝和血中的分布较水溶液有明显提高,30min时药物在肝中的浓度是水溶液的12倍,相对靶向效率为360%。结论SLN明显改变了苦参素的药动学行为,使消除变慢,生物利用度增加。苦参素SLN具有明显趋肝性,可靶向于肝,延长药物在血和肝中的滞留时间。

Pharmacokinetics and Tissue Distribution of Oxymatrine-SLN

OBJECTIVE To study the pharmacokinetics and tissue distribution of oxymatrine-SLN in animal and investigate the liver targeting effect of oxymatrine-SLN. METHODS Oxymatrine-SLN composed of oxymatrine, phospholipid and stearic acid were prepared by “emulsion- evaporation- solidified at low temperature” process. The average diameter of the particles was 104 nm, Zeta potential was -32.6 mV, and encapsulation efficiency was 81.0%. The pharmacokinetics of rats after intravenous administration of oxymatrine-SLN and oxymatrine solution 100 mg·kg^-1 was studied and the concentrations of oxymatrine in plasma, liver, lung, heart, spleen and kidney of mice were determined after intravenous administration 100 mg·kg^-1 in mice.RESULTS The plasma concentration-time curves were discribed by a two-compartment model. The t_1/2β of oxymatrine-SLN group was 5.5 times longer than oxymatrine solution group and the AUC of oxymatrine-SLN group was increased by 3.9 times compared with oxymatrine solution group. The tissue distribution of oxymatrine-SLN was different from that of free oxymatrine. The mean content of oxymatrine in liver at 30 min of oxymatrine-SLN group was 12 times greater than that of the oxymatrine solution group. Compared with oxymatrine solution, the relatively target efficiency to liver tissue was 360%.CONCLUSION It is demonstrated that oxymatrine-SLN has selective targeting to liver tissue and the liver targeted oxymatrine-SLN seem to have significant advantages and good development value.